Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 22, 2023

Abstract Macrophages exist in various tissues, several body cavities, and around mucosal surfaces are a vital part of the innate immune system for host defense against many pathogens cancers. possess binary M1/M2 macrophage polarization settings, which perform central role an array tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about signaling modulation yet to uncovered. In addition, clinical importance tumor-associated macrophages is becoming more widely recognized as significant progress has been made understanding their biology. Moreover, they integral tumor microenvironment, playing regulation wide variety processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, resistance chemotherapeutic checkpoint blockade immunotherapies. Herein, we discuss signaling, mechanical stresses modulation, metabolic pathways, mitochondrial transcriptional, epigenetic regulation. Furthermore, have broadly extended traps essential roles autophagy aging regulating functions. discussed recent advances macrophages-mediated autoimmune diseases tumorigenesis. Lastly, targeted therapy portray prospective targets therapeutic strategies health diseases.

Язык: Английский

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Immune cell-mediated features of non-alcoholic steatohepatitis

Nature reviews. Immunology, Год журнала: 2021, Номер 22(7), С. 429 - 443

Опубликована: Ноя. 5, 2021

Non-alcoholic fatty liver disease (NAFLD) includes a range of hepatic manifestations, starting with steatosis and potentially evolving towards non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma. NAFLD is major health burden, its incidence increasing worldwide. Although it primarily disturbed metabolism, involves several immune cell-mediated inflammatory processes, particularly when reaching the stage NASH, at which point inflammation becomes integral to progression disease. The cell landscape diverse steady state further evolves during NASH direct consequences for severity. In this Review, we discuss current concepts related role cells in onset NASH. A better understanding mechanisms by contribute pathogenesis should aid design innovative drugs target therapeutic options are limited. (NASH) serious chronic disorder prevalence Metabolic nature, also mobilizes system. Here, Huby Gautier knowledge regarding how subsets affect progression.

Язык: Английский

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Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

Cell Death and Disease, Год журнала: 2020, Номер 11(9)

Опубликована: Сен. 25, 2020

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic worldwide. NAFLD stages range from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) which can progress cirrhosis and hepatocellular carcinoma. One crucial events clearly involved in progression lipotoxicity resulting an excessive acid (FFA) influx hepatocytes. Hepatic occurs when capacity hepatocyte manage export FFAs as triglycerides (TGs) overwhelmed. This review provides succinct insights into molecular mechanisms responsible for NAFLD, including ER oxidative stress, autophagy, lipoapotosis inflammation. In addition, we highlight role CD36/FAT translocase pathogenesis. Up-to-date, it well known that CD36 increases FFA uptake and, liver, drives hepatosteatosis onset might contribute its NASH. Clinical studies have reinforced significance by showing increased content patients. Interestingly, circulating levels a soluble form (sCD36) are abnormally elevated patients positively correlate with histological grade hepatic steatosis. fact, induction translocation plasma membrane hepatocytes may be determining factor physiopathology Given all these data, targeting or some functional regulators promising therapeutic approach prevention treatment NAFLD.

Язык: Английский

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NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Окт. 7, 2020

Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms, and provides the reducing power for anabolic reactions redox balance. NADPH homeostasis regulated by varied signaling pathways several metabolic enzymes that undergo adaptive alteration cancer cells. The reprogramming of renders cells both highly dependent on this network antioxidant capacity more susceptible to oxidative stress. Modulating unique might be effective strategy eliminate these In review, we summarize current existing literatures homeostasis, including its biological functions, regulatory mechanisms corresponding therapeutic interventions human cancers, providing insights into implications targeting metabolism associated mechanism therapy.

Язык: Английский

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Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy

Antioxidants, Год журнала: 2021, Номер 10(2), С. 174 - 174

Опубликована: Янв. 26, 2021

Oxidative stress (OxS) is considered a major factor in the pathophysiology of inflammatory chronic liver diseases, including non-alcoholic disease (NAFLD). Chronic impairment lipid metabolism closely related to alterations oxidant/antioxidant balance, which affect metabolism-related organelles, leading cellular lipotoxicity, peroxidation, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Increased OxS also triggers hepatocytes pathways, inflammation fibrogenesis, contributing progression steatohepatitis (NASH). The antioxidant response, regulated by Nrf2/ARE pathway, key component this process counteracts oxidative stress-induced damage, restoration normal metabolism. Therefore, modulation response emerges as an interesting target prevent NAFLD development progression. This review highlights link between disturbed context NAFLD. In addition, emerging potential therapies based on effects their likely molecular targets are discussed.

Язык: Английский

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Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Antioxidants, Год журнала: 2020, Номер 9(12), С. 1279 - 1279

Опубликована: Дек. 15, 2020

Activated hepatic stellate cells (HSCs) and myofibroblasts are the main producers of extracellular matrix (ECM) proteins that form fibrotic tissue leads to fibrosis. Reactive oxygen species (ROS) can directly activate HSCs or induce inflammation programmed cell death, especially pyroptosis, in hepatocytes, which turn activates fibroblasts produce ECM proteins. Therefore, antioxidants nuclear factor E2-related factor-2 signaling pathway play critical roles modulating profibrogenic response. The master proinflammatory factors factor-κB (NF-κB) nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome may coordinate molecules such as interleukins 1β 18, effectively HSCs, large amounts Furthermore, NLRP3 pro-caspase 1, is upregulated by NF-κB, caspase induces pyroptosis via gasdermin activation HSCs. ROS central NF-κB pathways IκB (an inhibitor NF-κB) thioredoxin-interacting protein, respectively, thereby linking molecular mechanisms oxidative stress, Elucidating these pave way for development therapeutic tools interfere with specific targets.

Язык: Английский

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Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review

Frontiers in Medicine, Год журнала: 2021, Номер 8

Опубликована: Фев. 26, 2021

Non-alcoholic fatty liver disease (NAFLD) is a challenging caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory fibrotic progression, quite strictly linked lipotoxic injury from acids and/or wide variety their biologically active metabolites in context either two-hit or (more recent) parallel hits theory. An antioxidant defense system usually able protect hepatic cells damaging effects ROS, including those produced into gastrointestinal tract, i.e., by-products generated usual cellular metabolic processes, normal dysbiotic microbiota, diet through enhanced gut–liver axis. Oxidative originating imbalance ROS generation defenses under influence individual genetic epigenetic factors as well. Healthy physical activity have been shown be effective also with mechanisms, but compliance these lifestyles very low. Among several considered antioxidants, vitamin E has particularly studied; however, data are contradictory. Some studies natural polyphenols proposed for prevention treatment encouraging. Probiotics, prebiotics, diet, fecal microbiota transplantation represent new approaches targeting gut dysbiosis. In near future, precision medicine taking consideration environmental risk will likely assist further selecting that could work best specific patient.

Язык: Английский

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Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Авг. 13, 2022

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form NAFL, can be progressive and more susceptible to developing cirrhosis hepatocellular carcinoma. Currently, lifestyle interventions are most essential effective strategies for preventing controlling NAFL without development fibrosis. While there still limited appropriate drugs specifically treat NAFL/NASH, growing progress is being seen in elucidating pathogenesis identifying therapeutic targets. In this review, we discussed recent developments etiology prospective targets, as well pharmacological candidates pre/clinical trials patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, Importantly, evidence elucidates that disruption gut-liver axis microbe-derived metabolites drive NAFL/NASH. Extracellular vesicles (EVs) act signaling mediator, resulting accumulation, macrophage stellate cell activation, further promoting inflammation fibrosis progression during Targeting gut microbiota or EVs may serve new treatment Finally, other mechanisms, such therapy genetic approaches, also have enormous potential. Incorporating different mechanisms personalized medicine improve efficacy better benefit patients

Язык: Английский

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Different effects of nano- and microplastics on oxidative status and gut microbiota in the marine medaka Oryzias melastigma

Journal of Hazardous Materials, Год журнала: 2020, Номер 405, С. 124207 - 124207

Опубликована: Окт. 15, 2020

Язык: Английский

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Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy

Redox Biology, Год журнала: 2020, Номер 36, С. 101635 - 101635

Опубликована: Июль 8, 2020

Exercise and dietary intervention are currently available strategies to treat nonalcoholic fatty liver disease (NAFLD), while the underlying mechanism remains controversial. Emerging evidence shows that lipophagy is involved in inhibition of lipid droplets accumulation. However, it still unclear if exercise improve NAFLD through regulating lipophagy, how skeletal muscle can modulate metabolism liver. Moreover, associated with aging, little known about effect accumulation on aging process. Here vivo vitro models, we found reduced formation, decreased hepatic triglyceride induced by high-fat diet. enhanced activating AMPK/ULK1 inhibiting Akt/mTOR/ULK1 pathways respectively. Furthermore, stimulated FGF21 production muscle, followed secretion circulation promote via an AMPK-dependent pathway. Importantly, for first time, demonstrated exacerbated which was ameliorated inducing lipophagy. Our findings suggested a new promoting The study also provided support beneficial other metabolic organs such as FGF21-mediated AMPK dependent might be potential drug target caused dysfunction.

Язык: Английский

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